PMID: 

Occup Med (Lond). 2007 Oct ;57(7):518-24. Epub 2007 Aug 29. PMID: 17728306

Abstract Title: 

Occupational exposure to ionizing and non-ionizing radiation and risk of glioma.

Abstract: 

BACKGROUND: Although the aetiology of glioma is poorly understood, the higher incidence in males has long suggested an occupational cause.AIM: To investigate possible associations between occupational exposure to ionizing, ultraviolet (UV), radiofrequency (RF) and extremely low frequency (ELF) radiation and adult glioma risk.METHODS: Case-control study using histologically confirmed cases of glioma first diagnosed between 1987 and 1991 in Melbourne, Australia, matched by age, sex and postcode of residence. A detailed occupational history was obtained for each subject. Exposure to radiation was assessed using a Finnish job exposure matrix (FINJEM) for all the radiation types as well as self-reports and expert hygienist review for RF and ionizing radiation. For ELF and UV, gender-specific FINJEM analysis was performed.RESULTS: The study population consisted of 416 cases of glioma and 422 controls. The risk estimates given by FINJEM for ELF, RF and ionizing radiation were close to or below unity. Gender-specific analysis for UV showed odds ratios of 1.60 [95% confidence interval (CI) 0.95-2.69] and 0.54 (95% CI 0.27-1.07) for the highest exposed group of men and women, respectively (corresponding P value for trend was 0.03 and 0.04).CONCLUSIONS: We did not find evidence of an association between glioma and occupational exposure to ELF, RF and ionizing radiation. UV radiation was associated with increased glioma risk for men but this result could have been confounded by other predominantly male occupational and lifestyle exposures associated with high UV. Further investigation of UV radiation and glioma risk is suggested.

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PMID: 

Pathophysiology. 2012 Apr ;19(2):95-100. Epub 2012 Mar 27. PMID: 22458999

Abstract Title: 

Reported functional impairments of electrohypersensitive Japanese: A questionnaire survey.

Abstract: 

An increasing number of people worldwide complain that they have become electromagnetic hypersensitive (EHS). We conducted a questionnaire survey of EHS persons in Japan. The aim was to identify electromagnetic fields (EMF) and plausible EMF sources that caused their symptoms. Postal questionnaires were distributed via a self-help group, and 75 participants (95% women) responded. Reported major complaints were"fatigue/tiredness"(85%),"headache","concentration, memory, and thinking"difficulty (81%, respectively). Seventy-two per cent used some form of complementary/alternative therapy. The most plausible trigger of EHS onset was a mobile phone base station or personal handy-phone system (37%). Sixty-five percent experienced health problems to be due to the radiation from other passengers' mobile phones in trains or buses, and 12% reported that they could not use public transportation at all. Fifty-three percent had a job before the onset, but most had lost their work and/or experienced a decrease in income. Moreover, 85.3% had to take measures to protect themselves from EMF, such as moving to low EMF areas, or buying low EMF electric appliances. EHS persons were suffering not only from their symptoms, but also from economical and social problems.

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PMID: 

Circ J. 2019 Jul 25 ;83(8):1726-1736. Epub 2019 Jun 20. PMID: 31217391

Abstract Title: 

Withaferin A Prevents Myocardial Ischemia/Reperfusion Injury by Upregulating AMP-Activated Protein Kinase-Dependent B-Cell Lymphoma2 Signaling.

Abstract: 

BACKGROUND: Withaferin A (WFA), an anticancer constituent of the plant Withania somnifera, inhibits tumor growth in association with apoptosis induction. However, the potential role of WFA in the cardiovascular system is little-studied and controversial.Methods and Results:Two different doses of WFA were tested to determine their cardioprotective effects in myocardial ischemia/reperfusion (MI/R) injury through evaluation of cardiofunction in wild-type and AMP-activated protein kinase domain negative (AMPK-DN) gentransgenic mice. Surprisingly, cardioprotective effects (improved cardiac function and reduced infarct size) were observed with low-dose WFA (1 mg/kg) delivery but not high-dose (5 mg/kg). Mechanistically, low-dose WFA attenuated myocardial apoptosis. It decreased MI/R-induced activation of caspase 9, the indicator of the intrinsic mitochondrial pathway, but not caspase 8. It also upregulated the level of AMP-activated protein kinase (AMPK) phosphorylation and increased the MI/R inhibited ratio of Bcl2/Bax. In AMPK-deficient mice, WFA did not ameliorate MI/R-induced cardiac dysfunction, attenuate infarct size, or restore the Bcl2/Bax (B-cell lymphoma2/Mcl-2-like protein 4) ratio.CONCLUSIONS: These results demonstrated for the first time that low-dose WFA is cardioprotective via upregulation of the anti-apoptotic mitochondrial pathway in an AMPK-dependent manner.

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PMID: 

Mol Biol Rep. 2019 Jun 19. Epub 2019 Jun 19. PMID: 31218539

Abstract Title: 

Withania somnifera root powder protects againist post-traumatic stress disorder-induced memory impairment.

Abstract: 

Post-traumatic stress disorder (PTSD) is precipitated by exposure to severe traumatic events such as wars, natural disasters, catastrophes, or other traumatic events. Withania somnifera (WS) Dunal (family: Solanaceae) known traditionally as"Ashwaghanda"is used widely in ayurvedic medicine, and known to have positive role in neurodegenerative diseases. In this study, WS effect on impairment of memory due to PTSD was studied in animal models. Single-prolonged stress rat model, which consisted of restrain for 2 h, forced swimming for 20 min, rest for 15 min, and diethyl ether exposure for 1-2 min, was used to induce PTSD animals. The WS root powder extract was administered orally at a dose of 500 mg/kg/day. The radial arm water maze (RAWM) was used to assess spatial learning and memory. Enzymatic assays were used to evaluate changes in oxidative stress biomarkers in the hippocampus following treatments. The result showed that PTSD resulted in short- and long- term memory impairments. Administration of WS prevented this impairment of memory induced by PTSD. Furthermore, WS prevented PTSD inducedchanges in oxidative stress biomarker in the hippocampus. For quality assessment, the methanolic extract for WS was subjected to UHPLC analysis. A calibration curve for isowithanone as a marker compound was constructed. WS roots content of isowithanone was found to be 0.23% (w/w). In conclusion, WSadministration prevented PTSD induced memory impairment probably through preserving changes in antioxidant mechanisms in the hippocampus.

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PMID: 

Biochem Pharmacol. 2019 Aug 9. Epub 2019 Aug 9. PMID: 31404528

Abstract Title: 

Withaferin A: from Ayurvedic folk medicine to preclinical anti-cancer drug.

Abstract: 

Despite the recent successes of targeted cancer immuno-therapies, drug resistance and disease relapse remain a huge burden in cancer patient treatment. This has fueled renewed interest in natural product discovery to identify new pharmacophores for innovative cancer drug development. Reverse pharmacology approaches of Withania somnifera leaves and roots (alternatively also called Ashwagandha or Indian ginseng in traditional Ayurvedic and Unani folk medicine) have identified Withaferin A (WA) as the most bioactive compound for treatment of inflammatory ailments, supporting traditional use of their corresponding extracts in indigenous medicine. In this review we summarize preclinical in vivo evidence for therapeutic cancer applications of WA and provide a biochemical framework of its polypharmaceutical effects against cancer hallmarks.

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PMID: 

Food Chem. 2019 Nov 30 ;299:125119. Epub 2019 Jul 2. PMID: 31295638

Abstract Title: 

Enhancing antioxidant and antimicrobial activity of carnosic acid in rosemary (Rosmarinus officinalis L.) extract by complexation with cyclic glucans.

Abstract: 

Of all the active compounds in rosemary extract, carnosic acid (CaA) has the most potent antimicrobial and antioxidant activity; however, its low solubility limits its applications. We developed complexing systems using cycloamylose (CA), branched dextrin (BD), andβ-cyclodextrin (βCD) to improve the solubility of CaA and compared it to the use of maltodextrin (MD). The complexes formed with CA, BD, βCD, and MD improved the water solubility of CaA by as much as 2.8-fold, 2.1-fold, 1.75-fold, and 2.06-fold, respectively. The antioxidant capacity of CaA in aqueous solutions was also enhanced in the complexes due to the increased water solubility. Interestingly, the antimicrobial activity was improved more dramatically upon complexation with CA (7.27-fold) compared to the improvement when complexed with BD (4.82-fold), βCD (2.87-fold), and MD (3.83-fold). This may be due to the improvement of the antimicrobial potential of the functional groups of CaA by complexation with flexible cyclic glucans.

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PMID: 

J Food Biochem. 2019 Jul ;43(7):e12905. Epub 2019 May 20. PMID: 31353725

Abstract Title: 

Ameliorative impact of cold-pressed Rosmarinus officinalis oil against liver toxicity and genotoxic effects in streptozotocin-induced diabetic rats and their offspring.

Abstract: 

Diabetes mellitus (DM) is a chronic, lifelong condition threatening human health. Rosmarinus officinalis oil (RO) could have a future role in DM therapy. This study evaluated the composition and antioxidative potential of RO. Antidiabetic traits of RO in streptozotocin (STZ)-induced diabetic rats was also studied considering the ameliorative impact against embryogenesis defects using in vitro and in vivo biochemical, histological, and genetic assays. RO was investigated for fatty acids and bioactive compounds (tocols and total phenolic compounds), and antiradical potential against DPPHradicals. The genetic effects were investigated using comet assay and DNA fragmentation test. DM was induced to albino rats by injecting 60 mg/kg of STZ, while RO (100 mg/kg b.w.) was administered. The pregnant animals were divided into four groups; control (C), RO-treated (RO), diabetic (D), and combined diabetic with RO-treated (D-RO). The study was conducted for 180 days. In RO, the contents of polyunsaturated fatty acids, monounsaturated fatty acids, and saturated fatty acids were 42.3%, 41.7%, and 15.8%, respectively. The levels of α-, β-, γ-, and δ-tocopherols were 280, 20, 1,025, and 35 mg/100 g RO, respectively. RO contained 7.2 mg GAE/g of total phenolic compounds (TPC), while RO quenched 70% of DPPHradicals. While glucose levels reached the highest in DM rats, treating STZ-induced diabetic animals with RO-resoluted serum glucose levels. RO reduced the highest levels of serum chemistry parameters were recorded in DM animals. Histological photographs of maternal and fetus liver exhibited degenerated hepatic cells and congestion central vein. Comet cells and DNA fragments were significantly decreased in D-RO group comparing to the DM group. RO exhibited antidiabetic capabilities, and thus, it could be utilized as a functional ingredient in novel foods, nutraceuticals, and dietary supplements for diabetic patients. PRACTICAL APPLICATIONS: RO is rich in bioactive phytochemicals (tocols and phenolic compounds) with antiradical and antihyperglycemic capabilities. Tocols and phenolics are active in radical scavenging of reactive nitrogen species (i.e., peroxynitrite and nitrogen dioxide), and in the prevention of DNA bases nitration. Our results demonstrated that RO could improve the disturbed metabolism of carbohydrate in STZ-diabetic animals. The potential mode of action of bioactive compounds in RO most likely encompasses the intracellular pathway involved in glucose homeostasis or insulin signaling. In addition, the suppression of oxidative stress by phenolic compounds could provide to the antidiabetic impacts of RO. Our data supported that RO could be utilized to ameliorate DM. Protection with RO directed high protection of the maternal organs and offspring against the oxidative stress of diabetes due to the antihyperlipidemic effects and the antioxidant capabilities of RO.

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PMID: 

Cell Mol Biol (Noisy-le-grand). 2017 Aug 30 ;63(8):104-108. Epub 2017 Aug 30. PMID: 28886322

Abstract Title: 

Carnosol inhibits Hedgehog signaling pathway in both LNCaP and DU145 prostate cancer cell lines.

Abstract: 

To investigate the effect of carnosol on the Hedgehog (HH) signaling pathway in human hormone-dependent prostate cancer cell line LNCaP and hormone-independent prostate cancer cell line DU145. The expression levels of glioma-associated oncogene homolog 1 (Gli1) and Sonic hedgehog (Shh) in human prostate cancer tissues were detected by immunohistochemistry. After treated with carnosol (0.25-16μmol/L), the cell survival of LNCaP and DU145 cells were detected by MTT assay. The expression levels of Gli1 and Shh mRNA and protein in the two cells were detected by qRT-PCR and western blot, respectively. The apoptosis was determined by the caspase-3 activity assay. Results showed that Shh andGli1 were upregulated in cancer tissues. The inhibitory effect of carnosol on cell survival was enhanced with concentration, suggesting both LNCaP and DU145 cells were sensitive to carnosol. The inhibitory effects of carnosol on Gli1 and Shh mRNAs in the hormone-dependent LNCaP prostate cancer cellwas stronger than that in the hormone-independent DU145 prostate cancer cells. Carnosol downregulated the expression of Gli1 in nucleus, and Shh in cells. Greater carnosol concentration resulted in lower levels of Gli1 and Shh. Carnosol increased caspase-3 activity in a dose-dependent manner, suggesting that carnosol promotes cell apoptosis. Thus, carnosol can inhibit the proliferation and induce the apoptosis of prostate cancer cells in vitro, and its mechanism might be associated with the inhibiting of HH signaling pathway. Although the inhibitory effect of carnosol on hormone-dependent LNCaP prostate cancer cells is stronger than hormone-independent DU145 prostate cancer cells, carnosol might be a potential drug for hormone-independent prostate cancer.

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PMID: 

J Neurooncol. 2008 Jan ;86(1):71-8. Epub 2007 Jul 10. PMID: 17619826

Abstract Title: 

Cellular phone use and brain tumor: a meta-analysis.

Abstract: 

BACKGROUND: The dramatic increase in the use of cellular phones has generated concerns about potential adverse effects, especially the development of brain tumors. We conducted a meta-analysis to examine the effect of cellular phone use on the risk of brain tumor development.METHODS: We searched the literature using MEDLINE to locate case-control studies on cellular phone use and brain tumors. Odds ratios (ORs) for overall effect and stratified ORs associated with specific brain tumors, long-term use, and analog/digital phones were calculated for each study using its original data. A pooled estimator of each OR was then calculated using a random-effects model.RESULTS: Nine case-control studies containing 5,259 cases of primary brain tumors and 12,074 controls were included. All studies reported ORs according to brain tumor subtypes, and five provided ORs on patients with>or =10 years of follow up. Pooled analysis showed an overall OR of 0.90 (95% confidence interval [CI] 0.81-0.99) for cellular phone use and brain tumor development. The pooled OR for long-term users of>or =10 years (5 studies) was 1.25 (95% CI 1.01-1.54). No increased risk was observed in analog or digital cellular phone users.CONCLUSIONS: We found no overall increased risk of brain tumors among cellular phone users. The potential elevated risk of brain tumors after long-term cellular phone use awaits confirmation by future studies.

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PMID: 

Biochem Cell Biol. 2018 12 ;96(6):769-776. Epub 2018 Jun 29. PMID: 29958095

Abstract Title: 

Carnosol suppresses interleukin-6 production in mouse lungs injured by ischemia-reperfusion operation and in RAW264.7 macrophages treated with lipopolysaccharide.

Abstract: 

Carnosol is a naturally occurring herbal compound, known for its antioxidative properties. We previously found that carnosol protected mouse lungs from ischemia-reperfusion injury in ex vivo cultures. To elucidate the molecular mechanisms underpinning carnosol-mediated lung protection, we analyzed modes of interleukin-6 (IL-6) gene expression, which is associated with lung ischemia-reperfusion injury. Microarray analysis of mouse lungs suggested that IL-6 mRNA levels were elevated in the mouse lungs subjected to clamp-reperfusion, which was associated with elevated levels of other inflammatory modulators, such as activating transcription factor 3 (ATF3). Carnosol pretreatment lowered the IL-6 protein levels in mouse lung homogenates prepared after the clamp-reperfusion. On the other hand, the ATF3 gene expression was negatively correlated with that of IL-6 in RAW264.7 cells. IL-6 mRNA levels and gene promoter activities were suppressed by carnosol in RAW264.7 cells, but rescued by ATF3 knockdown. When RAW264.7 cells were subjected to hypoxia-reoxygenation, carnosol treatment lowered oxygen consumption after reoxygenation, which was coupled with a correlation with a transient production of mitochondrial reactive oxygen species and following ATF3 gene expression. These results suggest that carnosol treatment could be a new strategy for protecting lungs from ischemia-reperfusion injury by modulating the ATF3-IL-6 axis.

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